tbuckley/cabot-search huggingface dataset:
Impact of Vision Impairment and Ocular Morbidity and Their Treatment on Depression and Anxiety in Children
Authors: Dongfeng Li, Ving Fai Chan, Gianni Virgili, Prabhath Piyasena, Habtamu Negash, Noelle Whitestone, Sara O’Connor, Baixiang Xiao, Mike Clarke, David H. Cherwek, Manpreet K. Singh, Xinshu She, Huan Wang, Matthew Boswell, S. Grace Prakalapakorn, Jennifer L. Patnaik, Nathan Congdon
Journal: Ophthalmology (2022)

This systematic review and meta-analysis summarizes existing evidence to establish whether vision impairment, ocular morbidity, and their treatment are associated with depression and anxiety in children.Understanding and quantifying these associations support early detection and management of mental health symptoms in children with vision impairment and ocular morbidity. Additionally, this review provides evidence in favor of insurance coverage for timely strabismus surgery.We searched 9 electronic databases from inception through February 18, 2021, including observational and interventional studies assessing whether vision impairment, ocular morbidity, or both and their treatment are associated with depression, anxiety, or both in children. We used narrative synthesis and meta-analysis with the residual maximum likelihood method. A protocol was registered and published on The International Prospective Register of Systematic Reviews (identifier: CRD42021233323).Among 28 992 studies, 28 956 studies (99.9%) were excluded as duplicates or unrelated content. Among 36 remaining studies, 21 studies (58.3%) were observational studies concerning vision impairment, 8 studies (22.2%) were observational studies concerning strabismus, and 7 studies (19.4%) were interventional studies. Vision impaired children demonstrated significantly higher scores of depression (standard mean difference [SMD], 0.57; 95% confidence interval [CI], 0.26-0.89; 11 studies) and anxiety (SMD, 0.62; 95% CI, 0.40-0.83; 14 studies) than normally sighted children. In particular, children with myopia demonstrated higher scores of depression (SMD, 0.58; 95% CI, 0.36-0.81; 6 studies) than normally sighted children. Strabismus surgery significantly improved symptoms of depression (SMD, 0.59; 95% CI, 0.12-1.06; 3 studies) and anxiety (SMD, 0.69; 95% CI, 0.25-1.14; 4 studies) in children.Among children, vision impairment is associated with greater symptoms of depression and anxiety. Surgical treatment of strabismus improved these symptoms. Further randomized controlled trials exploring the impact of public health measures for myopia correction on mental health in children are needed. Scaling up access to strabismus surgery could improve the mental health of affected children.
Maternal gut microbiome–induced IgG regulates neonatal gut microbiome and immunity
Authors: Katherine Z. Sanidad, Mohammed Amir, Aparna Ananthanarayanan, Anvita Singaraju, Nicholas B. Shiland, Hanna S. Hong, Nobuhiko Kamada, Naohiro Inohara, Gabriel Núñez, Melody Y. Zeng
Journal: Science Immunology (2022)

The gut microbiome elicits antigen-specific immunoglobulin G (IgG) at steady state that cross-reacts to pathogens to confer protection against systemic infection. The role of gut microbiome–specific IgG antibodies in the development of the gut microbiome and immunity against enteric pathogens in early life, however, remains largely undefined. In this study, we show that gut microbiome–induced maternal IgG is transferred to the neonatal intestine through maternal milk via the neonatal Fc receptor and directly inhibits Citrobacter rodentium colonization and attachment to the mucosa. Enhanced neonatal immunity against oral C. rodentium infection was observed after maternal immunization with a gut microbiome–derived IgG antigen, outer membrane protein A, or induction of IgG-inducing gut bacteria. Furthermore, by generating a gene-targeted mouse model with complete IgG deficiency, we demonstrate that IgG knockout neonates are more susceptible to C. rodentium infection and exhibit alterations of the gut microbiome that promote differentiation of interleukin-17A–producing γδ T cells in the intestine, which persist into adulthood and contribute to increased disease severity in a dextran sulfate sodium–induced mouse model of colitis. Together, our studies have defined a critical role for maternal gut microbiome–specific IgG antibodies in promoting immunity against enteric pathogens and shaping the development of the gut microbiome and immune cells in early life.
Uveal melanoma: Real-world analysis of immune checkpoint inhibitors efficacy and lymphocyte-to-monocyte ratio as a biomarker of response.
Authors: Antoine Desilets, Chloe Beland, Valerie Hladky, Steph A. Pang, Arielle Elkrief, Andreea Stepanov, Bertrand Routy, Karl Belanger, Wilson H. Miller, Olivier Larochelle, Rahima Jamal
Journal: Journal of Clinical Oncology (2022)

e21590 Background: Uveal melanoma (UM) is a rare subtype of melanoma. Real-world data is needed to guide management since patients with advanced UM were excluded from immune checkpoint inhibition (ICI) phase III clinical trials. Lymphopenia and elevated monocyte count, which represents a surrogate marker of systemic inflammation and a source of pro-angiogenic tumor-associated macrophages (TAM), have been associated with poor treatment outcomes in various solid tumors. We sought to characterize ICI efficacy in patients with UM vs cutaneous melanoma (CM) and to investigate pre-treatment lymphocyte-to-monocyte ratio (LMR) as a biomarker of response. Methods: We conducted a multicentric cohort study across 3 academic centers in Canada. Best overall responses as per the investigators were recorded. Overall survival (OS) and progression-free survival (PFS) were compared using the log rank (Mantel-Cox) test, with univariate analyses performed using Cox proportional hazard regression model. Results: A total of 122 patients with metastatic melanoma were included, either UM (n = 60) or CM (n = 62). UM patients were treated either with anti-PD-1 monotherapy (69%) or combination with anti-CTLA-4 (31%). Median OS was 35.4 months for CM versus 8.0 months for UM (HR 0.38, 95%CI 0.24-0.60, p = 0.0001). Median PFS was 10.7 months for CM versus 3.5 months for UM (HR 0.38, 95%CI 0.22-0.65, p = 0.0001). Best overall response in the UM group was progressive disease (74%), stable disease (10%) or partial response (16%). In UM patients, higher baseline LMR (HR 0.48, 95%CI 0.24-0.97, p = 0.04) and presence of immune-related adverse events (HR 0.42, 95%CI 0.20-0.89, p = 0.02) were associated with improved OS in univariate analysis. In CM, such association with high LMR was not significant (HR 0.58, 95% 0.28-1.21, p = 0.10) unless excluding patients with corticosteroid-induced lymphopenia due to recently treated brain metastases (HR 0.42, 95%CI 0.19-0.92, p = 0.03). Conclusions: Advanced UM treated with ICI have inferior survival outcomes compared with cutaneous primaries. Higher pre-treatment LMR is associated with improved OS to ICI in UM patients and could represent a surrogate marker of immune activation. Our findings reinforce the need for new treatment strategies in UM.
Improved pathologic complete response rates for triple-negative breast cancer in the I-SPY2 Trial.
Authors: Douglas Yee, Rebecca Arielle Shatsky, Christina Yau, Denise M. Wolf, Rita Nanda, Laura van 't Veer, Donald A. Berry, Angela DeMichele, Laura Esserman
Journal: Journal of Clinical Oncology (2022)

591 Background: The I-SPY2 Trial evaluates multiple investigative agents in neoadjuvant breast cancer therapy with the primary endpoint of estimated pathologic complete response (pCR) rate. As a platform phase 2 trial it utilizes an adaptive design to compare new regimens with control chemotherapy (weekly paclitaxel followed by AC). Methods: Specific regimens are assigned based on clinically relevant signatures, including triple negative breast cancer (TNBC). Drug regimens graduate from the trial when the predicted pCR rate in any signature meets the pre-specified threshold of 85% probability of success in a hypothetical 300-patient, 1:1 randomized, phase 3 trial. The strong correlation between pCR rate and event free survival has been reported. To establish the benefit of administering investigational agents in combination with control weekly paclitaxel x 12 in TNBC, we report estimated pCR rates for the first 7 investigational agents. Results: TNBC accounted for 37% (363/987) of enrolled patients. Only veliparib and carboplatin (VC) and pembrolizumab (Pembro) met the graduation criteria for TNBC. However, compared to control chemotherapy, each drug tested in TNBC resulted in a numerically superior pCR rate compared to control. These findings imply that stratification of TNBC by response-predictive biomarkers may lead to improved pCR rates. For example, we have used gene expression profiling to further refine TNBC classification into Immune enhanced (Immune+), Immune-/DNA Repair Deficient (DRD)+, and Immune-/DRD- classes. TNBC identified as immune enhanced (63%) have an 89% pCR rate to pembrolizumab, while VC is less effective with pCR rate of 71%. Similarly, Immune-/DRD+ (11%) identifies TNBCs with a 80% pCR rate to VC, while pembrolizumab’s pCR rate in this group is only 33%. For tumors that are neither immune enhanced or DRD-positive (Immune-/DRD-; 25%) show numerically improved pCR rates for neratinib (20%), MK2206 (25%), ganitumab (24%), and ganetespib (22%) compared to control (12%). pCR rates for VC (10%) and pembrolizumab (20%) in this group were similar to drugs that did not graduate. For TNBC, many agents in I-SPY2 showed numerically improved pCR rates compared to conventional chemotherapy even when they did not meet our specified definition of graduation. Conclusions: Further refinement of TNBC signatures should yield improved therapeutic strategies while also sparing women unnecessary systemic therapy. Clinical trial information: NCT01042379. [Table: see text]
Update to living systematic review on covid-19 in pregnancy
Journal: BMJ (2022)

Update to living systematic review on covid-19 in pregnancyThis living systematic review on coronavirus disease 2019 (covid-19) by Allotey and colleagues (BMJ 2020;370:m3320) has been updated.For the latest update, visit doi:.This second update includes 435 studies (293 152 pregnant and recently pregnant women with covid-19), of which 244 were new additions to the review.The prevalence of covid-19 in pregnant and recently pregnant women remain consistent with our original review and first update of the living systematic review.Pregnant women continue to be at increased risk of severe covid-19.In addition to high body mass index, advancing maternal age, and non-white ethnic origin, evidence suggests that pre-existing comorbidities, and pregnancy specific conditions such as pre-eclampsia and gestational diabetes are risk factors for severe disease.More data are needed to robustly assess the association between pregnancy specific conditions and covid-19 related outcomes.
Plenary Session—The Patient Journey: Equity of Cancer Care
Authors: Thomas A. Farrington, Liz Margolies, Shonta Chambers, Maria D. Garcia-Jimenez, Alyssa A. Schatz, Carmen E. Guerra
Journal: Journal of the National Comprehensive Cancer Network (2022)

Although many people with cancer have benefited from the host of therapeutic and research advances across many different tumor types over the past decades. Not every patient with cancer is afforded the opportunity for such treatments, and there is an assortment of notable barriers to the delivery of equitable care for all. To address the complexity of this important issue in contemporary cancer care, a distinguished panel at the NCCN 2022 Annual Conference explored this topic from several different vantage points, including the patient perspective and the view from inside the LGBTQ+ community. In addition, several panel members explored the constructive steps and initiatives being taken in the clinical, research, and policy realms to improve access to care for all patients with cancer, as well as overall health equity.
Outpatient cancer rehabilitation services for gynecologic cancer survivors: Who participates, and do they benefit?
Authors: Mackenzi Pergolotti, Kelley C Wood, Jessica Bertram, Tiffany Kendig, Mary Hidde, Aliza L. Leiser, Alexandre Buckley De Meritens
Journal: Journal of Clinical Oncology (2022)

e18793 Background: Women with gynecologic cancers are likely to experience acute, late, or lasting functional impairments that impact ability to complete activities of daily living and quality of life. While cancer rehabilitation interventions (physical or occupational therapy, PT/OT) treat functional impairment, the use, impact, and acceptability of these services in community-based settings is unknown. We describe outpatient PT/OT services used by gynecologic cancer survivors and evaluate the impact and acceptability of these services using patient-reported outcome measures (PROM). Methods: This retrospective study included women with history of gynecologic cancer (via ICD-10 code) who: (1) received community-based outpatient cancer PT/OT services provided by a single institution in 5 geographic regions of the United States in 2019, and (2) completed a PROM at evaluation and discharge. Data was extracted from PT/OT medical charts. We calculated descriptive statistics for all available patient and rehabilitation characteristics (including age, cancer type, complexity-level of rehabilitation, interventions provided and number of visits). To evaluate pre-post rehabilitation change for each PROM, we used paired samples t-tests, then calculated pre-post effect size (Hedge’s g) and the proportion who achieved the minimal detectable change (MDC). We calculated median Net Promotor Score (NPS, 0-10) to determine acceptability. Results: Women who received rehabilitation (N = 84) were 64.63 ± 11.04 (range = 40.82 – 90.82) years old with predominant diagnoses of ovarian (n = 35, 41.7%) or endometrial (n = 27, 32.1%) cancer. Most attended PT (vs. OT) and completed 13 sessions ( IQR= 8.0 – 19.0). Seventeen different PROM were used. From pre- to post- rehabilitation, a significant improvement was seen in four PROM: Lower Extremity Functional Scale (LEFS; n= 20, M∆ = 12.88 ± 12.31, t(19) = 4.68, p = .00), Modified Fatigue Impact Scale (MFIS; n= 14, M∆ = 6.55 ± 9.69, t(13) = 2.53, p = .03), Patient-Specific Functional Scale (PSFS; n= 14, M∆ = 2.93 ± 2.31, t(13) = 4.72, p = .00), and Lymphedema Life Impact Scale (LLIS; n= 12, M∆ = 20.50 ± 20.61, t(11) = 3.45, p = .01). A large pre-post effect size (g ≥ 0.80) was observed for three PROM (17.6%), including: The PSFS ( n= 14, g = 1.47), LLIS, ( n= 12, g = 1.18), and Activities-specific Balance Confidence (ABC6; n= 3, g = 1.77). Overall, 54.8% (n = 46) patients achieved the PROM MDC. Median acceptability was 10.0 out of 10.0 ( n= 64, IQR = 9.75 – 10.0). Conclusions: For women with gynecologic cancers and functional impairment, cancer rehabilitation improved patient-reported function and was highly acceptable. Future research is needed to understand diagnosis-specific considerations and to optimize timing of rehabilitation.
The effect of donor age on pediatric kidney graft survival
Authors: L. Oomen, H. De Jong, A.H.M. Bouts, M.G. Keijzer-Veen, E.A.M. Cornelissen, L.L. De Wall, W.F.J. Feitz, C.M.H.H.T. Bootsma-Robroeks
Journal: European Urology (2022)
Real-world data on the clinical utility of a novel artificial intelligence-based computational method to support treatment decisions in gastrointestinal cancers.
Authors: Istvan Petak, Barbara Vodicska, Eniko Kispeter, Robert Doczi, Dora Tihanyi, Dora Lakatos, Anna Dirner, Matyas Vidermann, Reka Szalkai-Denes, Julia Deri, Maud Kamal, Richard Schwab, Christophe Le Tourneau
Journal: Journal of Clinical Oncology (2022)

e13616 Background: Several molecularly targeted agents (MTA) are registered in the same indication, even in the same line, to treat gastrointestinal (GI) cancers. Comprehensive molecular profiling is readily available for many patients, but only a few biomarkers are used to make clinical decisions between on-label MTAs. Most tumors harbor a combination of driver alterations potentially affecting the sensitivity to MTAs according to hundreds or thousands of evidence items that can explain the heterogeneous clinical response of individual patients to these therapies. We have developed an AI-based computational method, an automated, evidence-based reasoning framework, called digital drug assignment (DDA) to provide decision support based on the complete molecular profile for each patient. DDA has been shown to potentially improve treatment decisions in case of complex molecular profiles acquired in the SHIVA01 trial. In the present study, we analyzed the clinical utility of DDA in on-label treatment decisions in GI cancers. Methods: We analyzed the next-generation sequencing (NGS) data obtained using 50-591-gene panels of 239 patients with GI tract cancers from our everyday practice. Molecular profiles were uploaded to a DDA-based software system to calculate the aggregated evidence level (AEL) values of associated MTAs registered in the same indication of selected GI cancers. Decision support rate (DSR) was calculated as the percentage of patients where DDA could support clinical decisions based on the presence of genetic alterations associated with any of the available MTAs. Results: Targeted treatment options registered in the same indications and the DDA-based decision support rates (DSR) are shown in the table. For example, DDA could support the decision between cetuximab and bevacizumab based on NGS results in 47% of RAS/RAF wild-type colorectal cancer cases. Larger NGS panels yielded higher rates of decision support (44% vs 52% with gene panels under and over 300 genes, respectively). Conclusions: DDA-based computational reasoning can support molecular profile-based treatment decisions among different on-label MTAs in a clinically meaningful fraction of GI cancers.[Table: see text]
Clinical outcomes and life expectancy of patients with unplanned excisions of soft tissue sarcoma.
Authors: Sei Morinaga, Norio Yamamoto, Katsuhiro Hayashi, Akihiko Takeuchi, Shinji Miwa, Kentaro Igarashi, Hirotaka Yonezawa, Yohei Asano, Shiro Saito, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2022)

e23554 Background: As soft tissue sarcomas are rare, it is not uncommon that soft tissue sarcoma excision is performed without the required preoperative imaging, staging, or wide resection margins for sarcomas. This study investigated the characteristics of unplanned excision and analyzed the recurrence, life expectancy, and proper treatment for unplanned excision. Methods: Patients who underwent unplanned excision at another institution followed by additional wide excision at our hospital from January 2002 to December 2018 were identified. Forty-two patients met our criteria. The relationships between variables and oncological outcomes were statistically analyzed. Results: The mean age was 57.3 years (15–85 years). Sixty-nine percent (29 in 42) of tumors was in the subcutaneous tissue. Six tumors were located in the upper extremity, 24 in the lower extremity, and 12 in the trunk. Surgical margin after additional wide excision was positive in 10 cases and negative in 32 cases. Pathological examination of specimen showed 34 of 42 cases (80.9%) had residual tumor after primary tumor excision. Fourteen patients (33.3%) required reconstructions. Of the 42 patients, one had both preoperative MRI and biopsy, while nine patients underwent MRI only. Among them, only one patient had enhanced MRI. Ten patients had chemotherapy while no patient had radiotherapy over the follow-up period. The mean tumor size was 5.3 cm (0.8-20 cm). The unplanned excisions were performed by orthopaedic surgeons in 18 cases, by general surgeons in eight, by plastic surgeons in seven, by other surgeons in four. Four primary surgeries (9.5%) were performed in a sarcoma center. On multivariate analysis, positive surgical margin (HR 4.04, 95% CI 1.57-10.4, p &lt; 0.01) was significantly associated with lower 5-year recurrence-free survival. Conclusions: First, to reduce the number of cases of unplanned excision, it should be recognized that small, subcutaneous tumors may be malignant. Second, it is considered that the high recurrence rate with positive margins after additional wide excision might be due to failure to recognize the nature and extent of the tumor without enhanced MRI and biopsy before primary surgery. Finally, surgeons should be aware that positive margin at additional wide excision is an independent risk factor for local recurrence.[Table: see text]
Preliminary data from an ongoing phase 1 dose-escalation study of CCX559, an orally administered small molecule PD-L1 inhibitor, in patients with advanced solid tumors.
Authors: Gonzalo Tapia, Joanne Lundy, Gary Edward Richardson, Niky Zhao, Karen Ebsworth, Huibin Yue, Shichang Miao, Emil deGoma, Rita Jain, Thomas J. Schall, Kathleen Sullivan, Penglie Zhang, Paul L. de Souza
Journal: Journal of Clinical Oncology (2022)

2593 Background: The novel small molecule CCX559 is a highly potent and selective PD-L1 inhibitor that induces the dimerization and internalization of cell-surface PD-L1. CCX559, when orally administered in animal models, demonstrated anti-tumor efficacy, including the ability to induce complete responses (Li C, et al. Cancer Res 2021;81(13_Suppl): Abstract nr 1274). Safety pharmacology and toxicology studies in animals demonstrated an acceptable safety profile for CCX559. Taken together, the preclinical data supports the initiation of human trials in patients with advanced solid tumors. PD-(L)1 therapies have been shown to increase peripheral T cell activation and cytokines such as IFNγ and CXCL9 in patients (Herbst RS, et al. Nature.2014; 515(7528):563–567). Methods: This phase 1, first-in-patient, multicenter, open-label, dose-escalation study evaluates safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of CCX559 in patients with refractory, locally advanced or metastatic solid tumors. CCX559 is dosed orally once daily with a starting dose level of 30 mg. Dose escalation/de-escalation is based on the Bayesian Optimal Interval (BOIN) design. PBMC and plasma samples were collected from patients over the first 2 cycles (6 weeks) of treatment, and PD assays were performed, including measurement of cytokines and T cell proliferation. Results: As of February 1, 2022, one patient per cohort was enrolled at the 30 mg and 60 mg levels, and 9 patients were enrolled in the 120 mg dose cohort. Of the 11 patients enrolled, 5 patients (all 120 mg cohort) remain on treatment. No DLTs, treatment-related SAEs, or severe (Grade 3 or higher) treatment-related AEs have been reported. PD assays have been performed with samples from the 30 mg (n=1), 60 mg (n=1), and 120 mg (n=3) cohorts. Patients in all three cohorts showed increased peripheral CD4 and CD8 T cell proliferation starting in the first cycle (21 days) of treatment, as measured by Ki67 positivity. Increases in plasma IFNγ, CXCL9, CXCL10, and CXCL11 levels were observed, in particular in one patient (120 mg cohort) starting 15 days after treatment initiation. Conclusions: Initial results from the phase 1 dose-escalation study of CCX559 indicate on-target PD effects consistent with PD-L1 inhibition. Updated PD data, together with the safety and PK profile, will be presented. Clinical trial information: ACTRN12621001342808.